Our previous study demonstrated that recombinant mouse SCGB3A2 exhibits anti-fibrotic activity in bleomycin-induced pulmonary fibrosis model mouse. This was due to increased phosphorylation of STAT1 and expression of SMAD7, and decreased phosphorylation of SMAD2 and SMAD3, resulting in inhibition of the TGF beta signaling pathway, the hallmark of fibrosis, as examined in in vitro cell culture system using mouse lung primary fibroblasts. In the current study, we examined whether human SCGB3A2 exhibits similar anti-fibrotic activity to mouse SCGB3A2 in bleomycin-induced fibrosis in mice. In this mouse model, mice were intratracheally intubated bleomycin, followed by daily intravenous administration of recombinant mouse or human SCGB3A2 from day 7 for 5 days. After bleomycin administration, mice gradually lost weight during entire three weeks of the experimental period. Among three different doses of recombinant human SCGB3A2 tried (a total of 25, 50, and 100 microgram per mouse), mice administered 25 microgram SCGB3A2 showed less weight loss as compared with PBS control while with the other two doses, mice lost more weights. Both mouse and human SCGB3A2 at a dose of 25 microgram per mouse, were similarly effective on preventing bleomycin-administered mice from losing weight. Further, the number of inflammatory cells such as macrophages, neutrophils, monocyte and lymphocytes in bronchoalveolar lavage fluid, a percentage of fibrotic areas of lung histological sections, and the lung expression of various collagen genes such as Col1a1, 3a1, 4a1, 5a2, and 2a1, as determined by qRT-PCR, were all significantly lower at similar levels in mice treated with either mouse or human SCGB3A2 as compared to control. These results demonstrated that human SCGB3A2 is as effective as mouse SCGB3A2 in interfering fibrosis from progressing in bleomycin-induced pulmonary fibrosis model. This result further suggested that human and mouse SCGB3A2 may share a similar receptor, assuming that SCGB3A2 action is through a cell surface receptor specific to SCGB3A2. The fact that human SCGB3A2 functions as anti-fibrotic agent in mouse suggests that human SCGB3A2 may indeed be functional as anti-fibrotic agent in humans, leading to a potentially promising use of SCGB3A2 as a drug to treat pulmonary fibrosis.